Interleukin 26 (IL-26) also known as AK155 is a 19-kDa α-helical protein that belongs to the IL-20 cytokine family. IL-26 was first identified in herpesvirus saimiri-transformed T cells, and subsequently found to be conserved in most vertebrate species but absent in mice. Like other TH17 cytokines, IL-26 is highly expressed in psoriatic skin lesions (Wilson N J et al, Nat Immunol 2007, 8(9): 950-957), colonic lesions from patients with inflammatory bowel disease (Dambacher J, et al, Gut 2009, 58(9): 1207-1217), and synovia of rheumatoid arthritis patients (Corvaisier M, et al, PLoS Biol 2012, 10(9): e100139) and is strongly associated with inflammatory activity. A risk locus containing the IL-26 gene and single nucleotide polymorphisms (SNPs) within the IL26 gene region were associated with multiple sclerosis (Goris A, et al, Genes Immun 2001, 2(5): 284-286), rheumatoid arthritis (Vandenbroeck K, et al, Arthritis Rheum 2003, 48(10): 2773-2778) and inflammatory bowel disease (Silverberg M S, et al, Nat Genet 2009, 41(2): 216-220) suggesting a particularly important role of IL-26 in TH17-mediated inflammatory disease.
IL-26 was shown to signal through the IL-10R2-IL-20R1 heterodimeric receptor expressed exclusively by epithelial cells (Hor S, et al, J Biol Chem 2004, 279(32): 33343-33351 and, Sheikh F, et al, J Immunol 2004, 172(4): 2006-2010). Via its receptor, IL-26 was found to inhibit the proliferation of intestinal epithelial cells and, in parallel, to induce expression of immunosuppressive IL-10 but also the pro-inflammatory cytokines TNF and IL-8.
Furthermore, IL-26 and other interleukins such as IL-17A, IL-17F, IL-21, IL-22 are produced by Human T helper 17 (TH17) cells, a subset of T cell that drive inflammatory responses by producing and IL-26 (Wilson N J, et al, Nat Immunol 2007, 8(9): 950-957). Defective TH17 responses in patients deficient in the transcription factor STAT3 have been associated with increased susceptibility to Staphylococcus aureus and S. pyogenes infections (Ma C S, et al, J Exp Med 2008, 205(7): 1551-1557) indicating that this T cell subset plays a major role in the defense against extracellular bacterial infections particularly in the skin and mucosal surfaces. On the other hand, excessive TH17 cell responses drive chronic inflammation and the development of autoimmunity in predisposed individuals. TH17-associated cytokines were indeed associated with disease activity and found to be increased in the skin of psoriasis, in the intestine of Crohn's disease, in the brain of multiple sclerosis and the synovium of rheumatoid arthritis and ankylosing spondylitis patients (Gaffen S L et al, Nature reviews Immunology 2014, 14(9): 585-600).
US 2003/0073199 A1 (DNAX RESEARCH, INC.) discloses purified genes encoding a cytokine from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding this molecule are provided. Methods of using said reagents and diagnostic kits are also provided. The document further provides a method of treating a patient having an immune or inflammatory response by administering an effective dose of an antibody or binding partner for AK155.
WO 03/002717 (Schering Corporation.) and US 2003/0108958 (DNAX RESEARCH, INC.) relate to cells that express a recombinant AK155 receptor, methods for screening for agent that modulates the effects of an AK155 on an AK155 receptor, and for methods of treating disease using agents that modulate the interactions between an AK155 and an AK155 receptor. In these technologies the new function of IL-26 (AK155) is receptor-dependent and the developed antibodies are directed to the IL-26 receptor binding site.
Therefore, modulating (activating or blocking) the effects of IL-26 might represent an attractive modality for the treatment of inflammatory related diseases and/or bacterial infections. Further, in the management of inflammatory diseases and/or bacterial infections, there is a need for a modulator which is effective without eliciting secondary effects.